DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s claim listing filed September 27, 2026 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Claims 1-20 are pending in the application.
Restriction/Election
Applicant's election with traverse of Group I, claims 1-10 and 16-20, in the reply filed September 27, 2026 is acknowledged. Applicant traverses the restriction on the ground that claim 11 requires the stabilized analogue of claim 1 and thus cannot be practiced with a Protein X that is not cross-linked. Thus, according to applicant, the inventions of Groups I and II are not distinct.
This is not found persuasive. According to MPEP 806.05(h), a product and a process of using the product can be shown to be distinct inventions if either or both of the following can be shown: (A) the process of using as claimed can be practiced with another materially different product; or (B) the product as claimed can be used in a materially different process. Claim 11 is drawn to a method for treating or preventing Disease Y (process) by administering the stabilized analogue of claim 1 (product). In this case, the process can be practiced with another materially different product, such as any other product that can be administered to treat Disease Y, e.g., Protein X that is not cross-linked. Also, the stabilized analogue of claim 1 can be used in a materially different process, e.g., the stabilized analogue of claim 1 can be used as an antigen in a method for eliciting an antibody to Protein X.
Applicant further traverses the restriction on the ground that there would be no serious burden on the examiner to search and examine claim 11 with the claims of Group I because the search for the invention of Group I necessarily encompasses the method of claim 11.
This is not found persuasive at least because the inventions require a different field of search, e.g., searching different classes/subclasses and employing different search strategies or search queries for the additional limitations of claim 11.
The requirement is still deemed proper and is therefore made FINAL.
Claims 11-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant's election with traverse of species A4), first X protein is Tau, species B4), second protein X is Tau, species C1), the compound is 1,2-dithiolane, and species D2), the stabilized analogue has increased activity as compared to Protein X, in the reply filed September 27, 2026 is acknowledged. Applicant traverses the requirement for species election D on the ground that the search of the stabilized analogue of claim 1 will necessarily retrieve prior art to its activity and thus, a co-extensive search of species D1) and D2) would not require a serious burden on the examiner.
This is not found persuasive. Claim 9, corresponding to species D1), is drawn to the stabilized analogue of claim 1, wherein the stabilized analogue has reduced activity as compared to Protein X, and claim 10, corresponding to species D2), is drawn to the stabilized analogue of claim 1, wherein the stabilized analogue has increased activity as compared to Protein X. Products of identical chemical composition cannot have mutually exclusive properties (MPEP 2112.01.II) and thus, the structurally identical stabilized analogue of claim 1 cannot simultaneously have both reduced activity and increased activity as compared to Protein X. As such, a search for the stabilized analogue of claim 1 with reduced activity would not necessarily retrieve prior art directed to the stabilized analogue of claim 1 with increased activity and a separate keyword text search is required for each of species D1) and D2).
The requirement is still deemed proper and is therefore made FINAL.
Claims 3, 7, 9, 19, and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected species, there being no allowable generic or linking claim.
Claims 1, 2, 4-6, 8, 10, and 16-18 are being examined on the merits only to the extent the claims read on the elected subject matter.
Priority
This application is filed under 35 U.S.C. 120 as a continuation of U.S. non-provisional application no. 18/057,854, filed November 22, 2022, now abandoned, which is filed under 35 U.S.C. 120 as a continuation of U.S. non-provisional application no. 16/885,741, filed on May 28, 2020, now abandoned, which is filed under 35 U.S.C. 120 as a continuation of U.S. non-provisional application no. 15/753,319, filed on February 18, 2018, now U.S. Patent No. 10,711,261, which is filed under 35 U.S.C. 371 as a national stage of international application PCT/US2016/047395, filed on August 17, 2016, which claims domestic priority under 35 U.S.C. 119(e) to U.S. provisional application no. 62/206,316, filed on August 18, 2015.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on September 27, 2026 is in compliance with the provisions of 37 CFR 1.97 and has been considered by the examiner.
Specification/Informalities
Applicant is requested to update the status of application no. 18/057,854 in the “Cross-Reference to Related Applications” section of the specification (see specification amendment filed January 22, 2025). According to USPTO records, application no. 18/057,854 is now abandoned.
Drawing Figures
According to 37 CFR 1.84(u):
(u) Numbering of views.
(1) The different views must be numbered in consecutive Arabic numerals, starting with 1, independent of the numbering of the sheets and, if possible, in the order in which they appear on the drawing sheet(s). Partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. View numbers must be preceded by the abbreviation "FIG." Where only a single view is used in an application to illustrate the claimed invention, it must not be numbered and the abbreviation "FIG." must not appear.
(2) Numbers and letters identifying the views must be simple and clear and must not be used in association with brackets, circles, or inverted commas. The view numbers must be larger than the numbers used for reference characters.
The drawings filed on November 17, 2024 are objected to because view numbers must be preceded by the abbreviation "FIG." See 37 CFR 1.84(u)(1). Each of the drawing figures uses “Figure”, which should be replaced with “FIG.”
The drawings filed November 17, 2024 are also objected to because the partial views must be identified by the same number followed by a capital letter. The drawing figures 1-3 use a lower case letter, which should be replaced with a capital letter, and each sheet of drawing figure 4 must be identified by the same number followed by a capital letter, i.e., the two sheets of figure 4 should be identified as “FIG. 4A” and “FIG. 4B”, respectively.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 2, 4, 5, and 17 are objected to because of the following informalities:
Claims 2 and 17 are objected to in the recitation of “wherein the first Protein X and the second Protein X have at least 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology or identity to any one of the Protein X listed in Table 1” and in the interest of improving claim form, it is suggested that the noted phrase be amended to recite “wherein the amino acid sequence of the first Protein X and the amino acid sequence of the second Protein X have at least 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology or identity to the amino acid sequence of any one of the Protein X listed in Table 1.”
Claim 4 is objected to in the recitation of “wherein the first Protein X and the second Protein X are derived from the same Protein X shown in Table 1” and in the interest of improving claim form, it is suggested that the noted phrase be amended to recite “wherein the first Protein X and the second Protein X are the same Protein X.”
Claim 5 is objected to in the recitation of “wherein the first Protein X and the second Protein X are at least 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% homologous or identical to one another” and in the interest of improving claim form, it is suggested that the noted phrase be amended to recite “wherein the amino acid sequence of the first Protein X and the amino acid sequence of the second Protein X are at least 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% homologous or identical to one another.”
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1, 2, 4-6, 8, 10, and 16-18 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1 (claims 2, 4-6, 8, and 10 dependent therefrom), 2, 4 (claim 5 dependent therefrom), 16 (claim 18 dependent therefrom), and 17 are indefinite for referencing Table 1 for the first Protein X and the second Protein X. According to MPEP 2173.05(s), “[w]here possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table ‘is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.’" Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). Incorporating the first Protein X and/or the second Protein X by reference to Table 1 is not a necessity as the proteins (protein names and the corresponding Accession Numbers) can be incorporated into the claims.
Claims 2 and 17 are indefinite in the recitation of “have at least 80%...sequence homology or identity” because it is unclear from the claims and the specification as to the intended difference between sequence homology and sequence identity in the context of the claim. In the interest of advancing prosecution, it is suggested that applicant amend the noted phrase to recite “sequence identity.”
Claim 5 is indefinite in the recitation of “are at least 80%...homologous or identical” because it is unclear from the claims and the specification as to the intended difference between sequence homology and sequence identity in the context of the claim. In the interest of advancing prosecution, it is suggested that applicant amend the noted phrase to recite “have at least 80%...sequence identity.”
Claim 10 is indefinite in the recitation of “the stabilized analogue has increased activity as compared to Protein X” because it is unclear as to the intended “activity” that is referenced in the claim. In the interest of advancing prosecution, it is suggested that applicant clarify the recited “activity.”
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2, 5, and 17 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 1 recites “the first Protein X…is listed in Table 1” and “the second Protein X…is listed in Table 1,” thus limiting the “the first Protein X” and “the second Protein X” to a “Protein X” listed in Table 1. Table 1 includes a corresponding Accession Number for each Protein X and according to the specification at paragraph [0022], “the Accession Number is unique identifier used in the art that provides sequence information for each protein listed in Column 1.”
Claim 2, which depends from claim 1, recites “wherein the first Protein X and the second Protein X have at least 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology or identity to any one of the Protein X listed in Table 1.”
Given that claim 1 limits the “the first Protein X” and “the second Protein X” to being listed in Table 1, and Table 1 discloses a corresponding Accession Number sequence for each Protein X, claim 2 does not further limit claim 1.
Claim 4 recites “wherein the first Protein X and the second Protein X are derived from the same Protein X shown in Table 1.”
Claim 5, which depends from claim 4, recites “wherein the first Protein X and the second Protein X are at least 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% homologous or identical to one another.”
Given that claim 1 limits the “the first Protein X” and “the second Protein X” to being listed in Table 1, and Table 1 discloses a corresponding Accession Number sequence for each Protein X, claim 5 does not further limit claim 4.
Claim 16 recites “the first Protein X…is listed in Table 1” and “the second Protein X…is listed in Table 1,” thus limiting the “the first Protein X” and “the second Protein X” to a “Protein X” listed in Table 1. Table 1 includes a corresponding Accession Number for each Protein X and according to the specification at paragraph [0022], “the Accession Number is unique identifier used in the art that provides sequence information for each protein listed in Column 1.”
Claim 17, which depends from claim 16, recites “wherein the first Protein X and the second Protein X have at least 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology or identity to any one of the Protein X listed in Table 1.”
Given that claim 16 limits the “the first Protein X” and “the second Protein X” to being listed in Table 1, and Table 1 discloses a corresponding Accession Number sequence for each Protein X, claim 17 does not further limit claim 16.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - Improper Markush Grouping
Claims 1, 2, 4-6, 8, 10, and 16-18 are rejected on the basis that they contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
Claims 1 (claims 2, 4-6, and 10 dependent therefrom), 8, and 16 (claims 17 and 18 dependent therefrom) recite alternatives of structurally distinct compounds for cross-linking a first Protein X and a second Protein X, i.e., the compounds of Formula I and Formula II in claims 1 and 16, and the compounds of Formula III and Formula IV in claim 8. The Markush groupings of claims 1, 8, and 16 are improper because the alternatives defined by each of the Markush groupings do not share both a single structural similarity and a common use. Claims 1, 8, and 16 are “Markush”-type claims that each recite a plurality of structurally distinct compounds for cross-linking a first Protein X and a second Protein X. A Markush claim may be rejected under the judicially approved “improper Markush grouping” doctrine when the claim contains an improper grouping of alternatively useable species. A Markush claim contains an “improper Markush grouping” if: (1) The species of the Markush group do not share a “single structural similarity,” or (2) the species do not share a common use.
The species of compounds recited in each of the Markush groupings do not share any “single structural similarity”, i.e., a structural similarity essential to the common use of the species. When an examiner determines that the species of a Markush group do not share a single structural similarity or do not share a common use, then a rejection on the basis that the claim contains an “improper Markush grouping” is appropriate.
Claims 1, 2, 4 (claims 5, 6, 8, and 10 dependent therefrom), 16 (claim 18 dependent therefrom), and 17 recite alternatives of structurally and functionally distinct proteins, i.e., a first Protein X listed in Table 1 and a second Protein X listed in Table 2. The Markush groupings of claims 1, 2, 4, 16, and 17 are improper because the alternatives defined by each of the Markush groupings do not share both a single structural similarity and a common use. Claims 1, 2, 4, 16, and 17 are “Markush”-type claims that each recite a plurality of structurally and functionally distinct proteins. A Markush claim may be rejected under the judicially approved “improper Markush grouping” doctrine when the claim contains an improper grouping of alternatively useable species. A Markush claim contains an “improper Markush grouping” if: (1) The species of the Markush group do not share a “single structural similarity,” or (2) the species do not share a common use.
The species of proteins recited in each of the Markush groupings do not share any “single structural similarity”, i.e., a structural similarity essential to the common use of the species, and do not share a common use. When an examiner determines that the species of a Markush group do not share a single structural similarity or do not share a common use, then a rejection on the basis that the claim contains an “improper Markush grouping” is appropriate.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1, 2, 4-6, 8, 10, and 16-18 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
“The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors most relevant to the instant rejection are addressed in detail below.
The nature of the invention: According to the specification, “[t]here exists a need for a strategy for conferring specificity to drugs that target cysteine, in general, but pairs of cysteine, in particular” (paragraph [0007]) and “[w]e apply cyclic-disulfides to the stabilization of any one of the Protein X listed in Table 1 involved in diseases, such as, for example, Disease Y shown in Table 1….the disease that can be treated using the compounds disclosed herein, include, but are not limited to neurodegenerative disease (such as, for example, Parkinson’s Disease, ALS, Alzheimer’s Disease, Huntington's Disease, Epilepsy, Frontotemporal Dementia, and/or DMD), cancer, autoimmune disease and/or Celiac disease” (paragraph [0021]).
The breadth of the claims: Claims 1, 2, 4-6, 8, and 10 are drawn to (in relevant part) a stabilized analogue comprising a first Protein X and a second Protein X cross-linked to one another by 1,2-dithiolane, wherein
the first Protein X comprises a first cysteine residue and is tau protein having accession number NP_058519.3; and
the second Protein X comprises a second cysteine residue and is tau protein having accession number NP_058519.3.
Claims 16-18 are drawn to (in relevant part) a method comprising the step of contacting 1,2-dithiolane with a first Protein X and a second Protein X under conditions suitable for cross-linking the first Protein X to the second Protein X, thereby cross-linking the first Protein X to the second Protein X, wherein
the first Protein X comprises a first cysteine residue and is tau protein having accession number NP_058519.3; and
the second Protein X comprises a second cysteine residue and is tau protein having accession number NP_058519.3.
The state of the prior art; The level of one of ordinary skill; and The level of predictability in the art: According to MPEP 2164.03, “…what is known in the art provides evidence as to the question of predictability.” “[I]f one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art.”
Before the effective filing date, the reference of Agar et al. (WO 2014/078623 A2; cited on the IDS filed September 27, 2026) teaches applying cyclic disulfides including 1,2-dithiolane to cross-link cysteine residues and stabilize SOD-1 and DJ-1 polypeptides for use as therapeutics for treatment of ALS and Parkinson’s Disease, respectively (pp. 8-12 and 14).
The reference of Walker et al. (JBC 287:9591-9600, 2012; cited on the attached Form PTO-892) discloses that tau contains two cysteine residues and forms intramolecular disulfide bonds (p. 9591, Abstract).
The reference of Haque et al. (Amyloid 21:1-7, 2014; cited on the attached Form PTO-892) discloses that growing evidence has shown that tau intermolecular disulfide cross-linking is critical in generating tau oligomers that serve as a building block for higher-order aggregates, and that abnormal tau aggregates are presumed to be neurotoxic and are an important therapeutic target for multiple neurodegenerative disorders including Alzheimer’s disease (p. 1, Abstract). Haque et al. teach blocking the generation of disulfide cross-linked tau oligomers as a therapeutic strategy for prevention of abnormal tau aggregation.
Given that the art of record provides evidence that tau has two cysteine residues that form an intramolecular disulfide bond, one of skill in the art would have recognized a high level of unpredictability for tau oligomers to be stably cross-linked with 1,2-dithiolane. Moreover, even if one would have expected that tau oligomers can be stably cross-linked with 1,2-dithiolane, given that the art of record provides evidence that tau intermolecular disulfide cross-linking is critical in generating tau oligomers that serve as a building block for higher-order aggregates, and that abnormal tau aggregates are presumed to be neurotoxic and are an important therapeutic target for multiple neurodegenerative disorders including Alzheimer’s disease, one of skill in the art would have recognized that it is highly unpredictable and even highly unlikely that tau oligomers cross-linked with 1,2-dithiolane would be useful in accordance with the asserted utility, i.e., as a therapeutic for treating a disease. Rather, in view of the teachings of Haque et al. (supra), one would have expected that tau oligomers cross-linked with 1,2-dithiolane are neurotoxic.
The amount of direction provided by the inventor; The existence of working examples: The specification fails to disclose even a single working example of a stabilized analogue comprising oligomers of tau protein having accession number NP_058519.3 cross-linked to one another by 1,2-dithiolane and its use in accordance with the asserted utility as a therapeutic for treating a disease.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: It was not routine in the art to make a stabilized analog of tau as encompassed by the claims, particularly as there is no evidence of record that 1,2-dithiolane will cross-link and form a stabilized intermolecular dimer of oligomers of the tau protein having accession number NP_058519.3. It was also not routine in the art to use a stabilized analogue comprising oligomers of tau protein having accession number NP_058519.3 cross-linked to one another by 1,2-dithiolane in accordance with the asserted utility as a therapeutic for treating a disease.
In view of the scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability as evidenced by the art, and the amount of experimentation required, undue experimentation would be necessary for a skilled artisan to make and use the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Claims 1, 2, 4-6, 8, 10, and 16-18 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor had possession of the claimed invention.
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
MPEP § 2163 further states that “[s]atisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’"
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163.
Claims 1, 2, 4-6, 8, and 10 are drawn to (in relevant part) a stabilized analogue comprising a first Protein X and a second Protein X cross-linked to one another by 1,2-dithiolane, wherein
the first Protein X comprises a first cysteine residue and is tau protein having accession number NP_058519.3; and
the second Protein X comprises a second cysteine residue and is tau protein having accession number NP_058519.3.
Claims 16-18 are drawn to (in relevant part) a method comprising the step of contacting 1,2-dithiolane with a first Protein X and a second Protein X under conditions suitable for cross-linking the first Protein X to the second Protein X, thereby cross-linking the first Protein X to the second Protein X, wherein
the first Protein X comprises a first cysteine residue and is tau protein having accession number NP_058519.3; and
the second Protein X comprises a second cysteine residue and is tau protein having accession number NP_058519.3.
The specification fails to disclose the actual reduction to practice of even a single representative species of the recited stabilized analogue. Also, there is no evidence in the art of record that 1,2-dithiolane will cross-link and form a stabilized intermolecular dimer of the tau protein having accession number NP_058519.3. Rather, as stated above, the prior art reference of Walker et al. (supra) discloses that tau contains two cysteine residues and forms intramolecular disulfide bonds (p. 9591, Abstract). Given that the art of record teaches that the two cysteines of tau can form an intramolecular disulfide bond and there is no teaching in the art of record of a cyclic disulfide-mediated intermolecular cross-linking of two separate monomers of tau protein having accession number NP_058519.3, one of skill in the art would have recognized a high level of unpredictability that 1,2-dithiolane could form a stabilized analogue of tau proteins having accession number NP_058519.3 cross-linked to one another. Since the specification and art of record fail to disclose even a single representative species of the recited stabilized analogue and because the evidence of record indicates that the two cysteines of tau can form an intramolecular disulfide bond, the specification fails to sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicant was in possession of the claimed invention. As such, the specification fails to satisfy the written description requirement of 35 U.S.C. 112(a).
Conclusion
Status of the claims:
Claims 1-20 are pending.
Claims 3, 7, 9, 11-15, 19, and 20 are withdrawn from consideration.
Claims 1, 2, 4-6, 8, 10, and 16-18 are rejected.
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID J STEADMAN whose telephone number is (571)272-0942. The examiner can normally be reached Monday to Friday, 7:30 AM to 4:00 PM.
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/David Steadman/Primary Examiner, Art Unit 1656
